Clinical Leprechaunism associated with normal response of patient fibroblasts to IgF I, IgF II and Insulin

Abstract

Leprechaunism is a rare syndrome related to cell resistance to growth factors. The purpose of this study was to define the response of 4 year old girl to growth hormone (hgH) and to several growth factors. Diagnosis of leprechaunism was made on the basis of severe growth retardation at 4 years of age (L = 72,5 cm <5 SD ; W = 6.300 kg <5 SD), facial dysmorphism, absence of subcutaneous fat and history of hypoglycemia. hgH response to pharmacological stimuli was found lower than 5 ng/ml at 3 times. Basal levels of IgF I and IgF II were extremely low. When measured during hgH supplementation for 10 days (2 U/kg/day), IgF I and II peaked at the 5 day but still remained under the control values. After discontinuation of hgH, they decreased to basal levels in less than 10 days. The response of fibroblasts from the patient to several growth factors, judged by 3 H Thymidine incorporation and cell number, has been compared to the response of control fibroblasts. The responses did not differ for : normal human serum, fetal calf serum (1 to 30 %), IgF I, IgF II, Insulin (20 to 100 ng/ml), whole patient serum (5 %). When the effect of a control Plasma Derived Serum was compared to PDS of the patient, the fibroblasts exhibited a lower thymidine incorporation in the presence of 5 % patient PDS, with an apparent division blockage. In conclusion, to the difference of previous reports, fibroblasts of this patient seem to be responsive to IgF I, IgF II and Insulin. However, the patient plasma seems to lack some other stimulating factors which may act as division progression factors. We hypothetize that a defect of plasmatic factors which are not only IgF I, IgF II or Insulin may lead to the clinical features of leprechaunism.